Alagille syndrome (AGS) is a developmental disorder affecting multiple organ systems including liver, heart, eye, face and vertebrae. We have shown that mutations in the Jagged1 (JAG1) gene are responsible for AGS. Jagged1 encodes a ligand for the family of Notch receptors, and interactions between Notch receptors and their ligands have been shown to be critical for cell fate determination in early development of Drosophila and C. elegans. Similar to the involvement of Jagged1 in AGS, we hypothesize that alterations in genes encoding some of the Notch receptors or their ligands may lead to human or mouse phenotypes. In this direction we have identified and mapped the location of two additional genes encoding Notch ligands (Jagged2 and Delta1) in order to explore their role, if any, in human disease. In order to understand the role of Jagged genes in vertebrate development, we have also isolated and characterized 3 genes termed Jagged 1, 2 and 3 in Zebrafish. Their distinct expression pattern promises to provide a better understanding of their role in vertebrate development.